Ursolic acid (sometimes referred to as urson, prunol, malol, or 3β-hydroxyurs-12-en-28-oic acid), is a pentacyclic

triterpenoid Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squal ...

identified in the

epicuticular wax Epicuticular wax is a coating of wax covering the outer surface of the plant cuticle in land plants. It may form a whitish film or bloom on leaves, fruits and other plant organs. Chemically, it consists of hydrophobic organic compounds, mainly st ...

es of apples as early as 1920 and widely found in the peels of fruits, as well as in herbs and spices like

rosemary ''Salvia rosmarinus'' (), commonly known as rosemary, is a shrub with fragrant, evergreen, needle-like leaves and white, pink, purple, or blue flowers, native plant, native to the Mediterranean Region, Mediterranean region. Until 2017, it was kn ...

and

thyme Thyme () is the herb (dried aerial parts) of some members of the genus ''Thymus'' of aromatic perennial evergreen herbs in the mint family Lamiaceae. Thymes are relatives of the oregano genus '' Origanum'', with both plants being mostly indigen ...

Natural occurrence

Ursolic acid is present in many plants, such as ''

Mirabilis jalapa ''Mirabilis jalapa'', the marvel of Peru or four o'clock flower, is the most commonly grown ornamental species of ''Mirabilis'' plant, and is available in a range of colors. ''Mirabilis'' in Latin means wonderful and Xalapa, Jalapa (or Xalapa) is ...

'', as well as in many fruits and herbs used in daily life (e.g.

apple An apple is an edible fruit produced by an apple tree (''Malus domestica''). Apple trees are cultivated worldwide and are the most widely grown species in the genus '' Malus''. The tree originated in Central Asia, where its wild ancest ...

basil Basil (, ; ''Ocimum basilicum'' , also called great basil, is a culinary herb of the family Lamiaceae (mints). It is a tender plant, and is used in cuisines worldwide. In Western cuisine, the generic term "basil" refers to the variety also k ...

and holy basil,

bilberries Bilberries (), or sometimes European blueberries, are a primarily Eurasian species of low-growing shrubs in the genus '' Vaccinium'' (family Ericaceae), bearing edible, dark blue berries. The species most often referred to is ''Vaccinium myrti ...

cranberries Cranberries are a group of evergreen dwarf shrubs or trailing vines in the subgenus ''Oxycoccus'' of the genus ''Vaccinium''. In Britain, cranberry may refer to the native species ''Vaccinium oxycoccos'', while in North America, cranberry m ...

, elder flower,

peppermint Peppermint (''Mentha'' × ''piperita'') is a hybrid species of mint, a cross between watermint and spearmint. Indigenous to Europe and the Middle East, the plant is now widely spread and cultivated in many regions of the world.Euro+Med Plantb ...

lavender ''Lavandula'' (common name lavender) is a genus of 47 known species of flowering plants in the mint family, Lamiaceae. It is native to the Old World and is found in Cape Verde and the Canary Islands, and from Europe across to northern and easte ...

oregano Oregano (, ; ''Origanum vulgare'') is a species of flowering plant in the mint family Lamiaceae. It was native to the Mediterranean region, but widely naturalised elsewhere in the temperate Northern Hemisphere. Oregano is a woody perennial ...

hawthorn Hawthorn or Hawthorns may refer to: Plants * '' Crataegus'' (hawthorn), a large genus of shrubs and trees in the family Rosaceae * ''Rhaphiolepis'' (hawthorn), a genus of about 15 species of evergreen shrubs and small trees in the family Rosace ...

, and

prunes A prune is a dried plum, most commonly from the European plum (''Prunus domestica''). Not all plum species or varieties can be dried into prunes. A prune is the firm-fleshed fruit (plum) of '' Prunus domestica'' varieties that have a high so ...

). Apple peels contain large quantities of ursolic acid and related compounds.

Potential biochemical effects

A number of potential biochemical effects of ursolic acid have been investigated, but there has been no clinical study demonstrating benefits to human health. ''

In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'', ursolic acid inhibits the proliferation of various cancer cell types by inhibiting the

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respons ...

activation pathway, and may also decrease proliferation of cancer cells and induce

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...

. Ursolic acid has also been shown to inhibit JNK expression and IL-2 activation of JURKAT leukemic T Cells leading to the reduction in proliferation and T cell activation. Ursolic acid is a weak

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

(IC₅₀ = 32 μM), and has been shown to increase the amount of muscle and

brown fat Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). Brown adipose tissue is found in almost all mammals. Classification of brown fat refers to two distinct cell populations with si ...

and decrease white fat obesity and associated conditions when added to diets fed to mice. Under physiological concentrations, ursolic acid also induces eryptosis (the

-like suicidal cell death in defective red blood cells). It has been found to reduce

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...

and to stimulate muscular growth in mice, also shows a potential

cardioprotection Cardioprotection includes all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage. Cardioprotection encompasses several regimens that have shown to preserve function and viabilit ...

. In mice, ursolic acid induces neural regeneration after sciatic nerve injuries and recently found to have COVID preventative capabilities. More research in this recent finding is underway. In mice with chronic

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...

, ursolic acid has reduced further damage to neurons and helped rebuild the protective sheaths covering neurons, apparently by suppressing Th17 immune cells and activating precursor cells that mature into myelin-sheath-making cells, called

oligodendrocytes Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...

. Ursolic acid improves

domoic acid Domoic acid (DA) is a kainic acid-type neurotoxin that causes amnesic shellfish poisoning (ASP). It is produced by algae and accumulates in shellfish, sardines, and anchovies. When sea lions, otters, cetaceans, humans, and other predators eat c ...

-induced cognitive deficits in mice. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/

nuclear factor-κB Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...

-mediated inflammatory pathways in mice. Ursolic acid attenuates

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

-induced cognitive deficits in

mouse brain The mouse brain refers to the brain of Mus musculus. Various brain atlases exist. For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known onli ...

through suppressing p38/

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

mediated inflammatory pathways. Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of

senescent Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...

mice induced by D-galactose. Ursolic acid enhances mouse liver regeneration after partial hepatectomy. Ursolic acid enhances the cellular immune system and pancreatic

beta-cell Beta cells (β-cells) are a type of cell (biology), cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and fun ...

function in

streptozotocin Streptozotocin or streptozocin ( INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain can ...

-induced diabetic mice fed a high-fat diet. Ursolic acid increased skeletal muscle mass, as well as grip strength and exercise capacity, improved endurance, reduced the expression of the genes involved in the development of muscle atrophy, and decreased indicators of accumulated fatigue and exercise-induced stress. In rats, ursolic acid ameliorated high-fat diet-induced hepatic steatosis and improved metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease.

Uses

Ursolic acid can be found in plants that are used for cosmetics additives. It can serve as a starting material for synthesis of more potent bioactive derivatives, such as experimental antitumor agents.

References

{{reflist Triterpenes Hydroxy acids

Natural occurrence

Potential biochemical effects

Uses

See also

References